Subscribe to the gold package and get unlimited access to Shamra Academy
Register a new userQuantitative test of the barrier nucleosome model for statistical positioning of nucleosomes up- and downstream of transcription start sites
135
0
0.0
(
0
)
Ask ChatGPT about the research
No Arabic abstract
The positions of nucleosomes in eukaryotic genomes determine which parts of the DNA sequence are readily accessible for regulatory proteins and which are not. Genome-wide maps of nucleosome positions have revealed a salient pattern around transcription start sites, involving a nucleosome-free region (NFR) flanked by a pronounced periodic pattern in the average nucleosome density. While the periodic pattern clearly reflects well-positioned nucleosomes, the positioning mechanism is less clear. A recent experimental study by Mavrich et al. argued that the pattern observed in S. cerevisiae is qualitatively consistent with a `barrier nucleosome model, in which the oscillatory pattern is created by the statistical positioning mechanism of Kornberg and Stryer. On the other hand, there is clear evidence for intrinsic sequence preferences of nucleosomes, and it is unclear to what extent these sequence preferences affect the observed pattern. To test the barrier nucleosome model, we quantitatively analyze yeast nucleosome positioning data both up- and downstream from NFRs. Our analysis is based on the Tonks model of statistical physics which quantifies the interplay between the excluded-volume interaction of nucleosomes and their positional entropy. We find that although the typical patterns on the two sides of the NFR are different, they are both quantitatively described by the same physical model, with the same parameters, but different boundary conditions. The inferred boundary conditions suggest that the first nucleosome downstream from the NFR (the +1 nucleosome) is typically directly positioned while the first nucleosome upstream is statistically positioned via a nucleosome-repelling DNA region. These boundary conditions, which can be locally encoded into the genome sequence, significantly shape the statistical distribution of nucleosomes over a range of up to ~1000 bp to each side.
rate research
Read More
We present a statistical-mechanical analysis of the positioning of nucleosomes along one of the chromosomes of yeast DNA as a function of the strength of the binding potential and of the chemical potential of the nucleosomes. We find a significant density of two-level nucleosome switching regions where, as a function of the chemical potential, the nucleosome distribution undergoes a micro first-order transition. The location of these nucleosome switches shows a strong correlation with the location of transcription-factor binding sites.
DNA is a flexible molecule, but the degree of its flexibility is subject to debate. The commonly-accepted persistence length of $l_p approx 500,$AA is inconsistent with recent studies on short-chain DNA that show much greater flexibility but do not probe its origin. We have performed X-ray and neutron small-angle scattering on a short DNA sequence containing a strong nucleosome positioning element, and analyzed the results using a modified Kratky-Porod model to determine possible conformations. Our results support a hypothesis from Crick and Klug in 1975 that some DNA sequences in solution can have sharp kinks, potentially resolving the discrepancy. Our conclusions are supported by measurements on a radiation-damaged sample, where single-strand breaks lead to increased flexibility and by an analysis of data from another sequence, which does not have kinks, but where our method can detect a locally enhanced flexibility due to an $AT$-domain.
Positioning of nucleosomes along eukaryotic genomes plays an important role in their organization and regulation. There are many different factors affecting the location of nucleosomes. Some can be viewed as preferential binding of a single nucleosome to different locations along the DNA and some as interactions between neighboring nucleosomes. In this study we analyzed how well nucleosomes are positioned along the DNA as a function of strength of the preferential binding, correlation length of the binding energy landscape, interactions between neighboring nucleosomes and others relevant system properties. We analyze different scenarios: designed energy landscapes and generically disordered ones and derive conditions for good positioning. Using analytic and numerical approaches we find that, even if the binding preferences are very weak, synergistic interplay between the interactions and the binding preferences is essential for a good positioning of nucleosomes, especially on correlated energy landscapes. Analyzing empirical energy landscape, we discuss relevance of our theoretical results to positioning of nucleosomes on DNA emph{in vivo.}
Many biological assays are employed in virology to quantify parameters of interest. Two such classes of assays, virus quantification assays (VQA) and infectivity assays (IA), aim to estimate the number of viruses present in a solution, and the ability of a viral strain to successfully infect a host cell, respectively. VQAs operate at extremely dilute concentrations and results can be subject to stochastic variability in virus-cell interactions. At the other extreme, high viral particle concentrations are used in IAs, resulting in large numbers of viruses infecting each cell, enough for measurable change in total transcription activity. Furthermore, host cells can be infected at any concentration regime by multiple particles, resulting in a statistical multiplicity of infection (SMOI) and yielding potentially significant variability in the assay signal and parameter estimates. We develop probabilistic models for SMOI at low and high viral particle concentration limits and apply them to the plaque (VQA), endpoint dilution (VQA), and luciferase reporter (IA) assays. A web-based tool implementing our models and analysis is also developed and presented. We test our proposed new methods for inferring experimental parameters from data using numerical simulations and show improvement on existing procedures in all limits.
A quantitative description of the flagellar dynamics in the procyclic T. brucei is presented in terms of stationary oscillations and traveling waves. By using digital video microscopy to quantify the kinematics of trypanosome flagellar waveforms. A theoretical model is build starting from a Bernoulli-Euler flexural-torsional model of an elastic string with internal distribution of force and torque. The dynamics is internally driven by the action of the molecular motors along the string, which is proportional to the local shift and consequently to the local curvature. The model equation is a nonlinear partial differential wave equation of order four, containing nonlinear terms specific to the Korteweg-de Vries (KdV) equation and the modified-KdV equation. For different ranges of parameters we obtained kink-like solitons, breather solitons, and a new class of solutions constructed by smoothly piece-wise connected conic functions arcs (e.g. ellipse). The predicted amplitude and wavelengths are in good match with experiments. We also present the hypotheses for a step-wise kinematical model of swimming of procyclic African trypanosome.
Log in to be able to interact and post comments
comments
Fetching comments
Sign in to be able to follow your search criteria
